Horner Kristen A, Logan Mary Caroline, Fisher Trevor J, Logue Jordan B
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, United States.
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, United States.
Eur J Pharmacol. 2017 Feb 5;796:207-214. doi: 10.1016/j.ejphar.2017.01.001. Epub 2017 Jan 3.
The behavioral effects of methamphetamine (METH) are mediated by the striatum, which is divided into the patch compartment, which mediates limbic and reward functions, and the matrix compartment, which mediates sensorimotor tasks. METH treatment results in repetitive behavior that is related to enhanced relative activation of the patch versus the matrix compartment. The patch, but not the matrix compartment contains a high density of μ opioid receptors, and localized blockade of patch-based μ opioid receptors attenuates METH-induced patch-enhanced activity and repetitive behaviors. Numerous studies have examined patch-enhanced activity and the contribution of patch-associated μ opioid receptors to METH-induced repetitive behavior, but it is not known whether patch-enhanced activity occurs during METH-mediated reward, nor is it known if patch-based μ opioid receptors contribute to METH reward. The goals of this study were to determine if blockade of patch-based μ opioid receptors alters METH-induced conditioned place preference (CPP), as well activation of the patch and matrix compartments following METH-mediated CPP. A biased conditioning paradigm was used to assess CPP, and conditioning occurred over an 8-d period. Animals were bilaterally infused in the striatum with the μ-specific antagonist CTAP or vehicle prior to conditioning. Animals were tested for preference 24h after the last day of conditioning, sacrificed and the brains processed for immunohistochemistry. Blockade of patch-based μ opioid receptors reduced METH-induced CPP, and reduced patch-enhanced c-Fos expression in the striatum following METH-mediated CPP. These data indicate that patch-enhanced activity is associated with METH-mediated reward and patch-based μ opioid receptors contribute to this phenomenon.
甲基苯丙胺（METH）的行为效应由纹状体介导，纹状体分为介导边缘和奖赏功能的斑块区室以及介导感觉运动任务的基质区室。METH治疗会导致重复行为，这与斑块区室相对于基质区室的相对激活增强有关。斑块区室而非基质区室含有高密度的μ阿片受体，基于斑块的μ阿片受体的局部阻断会减弱METH诱导的斑块增强活动和重复行为。许多研究已经考察了斑块增强活动以及与斑块相关的μ阿片受体对METH诱导的重复行为的作用，但尚不清楚斑块增强活动是否发生在METH介导的奖赏过程中，也不清楚基于斑块的μ阿片受体是否对METH奖赏有作用。本研究的目的是确定基于斑块的μ阿片受体的阻断是否会改变METH诱导的条件性位置偏爱（CPP），以及在METH介导的CPP后斑块和基质区室的激活情况。使用有偏倚的条件化范式来评估CPP，条件化持续8天。在条件化之前，给动物双侧纹状体内注射μ特异性拮抗剂CTAP或溶剂。在条件化的最后一天后24小时对动物进行偏爱测试，然后处死动物并对大脑进行免疫组织化学处理。基于斑块的μ阿片受体的阻断降低了METH诱导的CPP，并降低了METH介导的CPP后纹状体内斑块增强的c-Fos表达。这些数据表明，斑块增强活动与METH介导的奖赏有关，且基于斑块的μ阿片受体促成了这一现象。
